Clinical Trial of Recombinant Herpes Zoster Vaccine (ZFA01 Adjuvant, CHO Cells)

Randomized, Multi-cohort, Controlled Phase I/II Clinical Trials Evaluating the Safety, Tolerability and Immunogenicity of Recombinant Herpes Zoster Vaccine (ZFA01 Adjuvant, CHO Cell) for Vaccination in Healthy Subjects Aged 40 Years and Above

A seamless Phase I/II trial evaluating the immunogenicity and safety of a recombinant herpes zoster ZFA01 adjuvanted vaccine (CHO cell) in healthy adults aged ≥40 years. Phase I (n=100): randomized, blinded, placebo-controlled, age/dose escalation across 4 cohorts. Phase II (n=400): randomized, open-label, active-controlled, with 1:1 or 1:1:1 allocation to two experimental groups and a positive control group across three age strata.

Study Overview

• Status: Recruiting
• Conditions: Herpes Zoster
• Intervention / Treatment: Biological: Low-dose adjuvanted recombinant zoster vaccine; Biological: High-dose adjuvanted recombinant zoster vaccine (0 and 30 days schedule); Biological: Low-dose adjuvant placebo; Biological: High-dose adjuvant placebo; Biological: High-dose adjuvanted recombinant zoster vaccine (0 and 60 days schedule); Biological: Zoster Vaccine Recombinant, Adjuvanted

Detailed Description

This trial adopts a seamless Phase I/II trial design, conducted in two stages: Phase I and Phase II. Phase I is an age/dose escalation stage, employing a randomized, blinded, placebo-controlled design to observe the safety of the vaccine. Phase II further expands the trial population to investigate the safety and immunogenicity of different immunization schedules, employing a randomized, open-label, active-controlled design with blinded assessment during the serological testing phase. The primary objective is to evaluate the immunogenicity and safety of the recombinant herpes zoster ZFA01 adjuvanted vaccine (CHO cell) in healthy populations aged 40 years and older.

Phase I evaluates the tolerability of different adjuvant doses in trial participants, enrolling a total of 100 participants in two age groups: 40-59 years and 60 years and older. Participants are enrolled in an age-escalation sequence (40-59 years → 60 years and older) and a dose-escalation sequence (from low-dose adjuvanted vaccine to high-dose adjuvanted vaccine), assigned to 4 cohorts at a 4:1 ratio.

Phase II aims to demonstrate the immunogenicity and safety of the vaccine in the target population, enrolling a total of 400 trial participants. Among them, 100 participants aged 40-49 years are randomized at a 1:1 ratio to experimental group 1 and experimental group 2; 210 participants aged 50-69 years and 90 participants aged 70 years and older are randomized at a 1:1:1 ratio to experimental group 1, experimental group 2, and the positive control group.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yi Mo, Principal Investigator; Phone Number: +86-13788686968; Email: moyi0415@qq.com

Study Locations

• China
  • Nanning
    • Guangxi, Nanning, China, 530022
      • Recruiting
      • Guangxi Zhuang Autonomous Region People's Hospital
      • Contact: Huijuan Li; Phone Number: 18877168857
    • Guangxi, Nanning, China, 530028
      • Recruiting
      • Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention
      • Contact: Yi Mo; Phone Number: 13788686968; Email: moyi0415@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Study participants must meet all of the following inclusion criteria:

  1. Aged 40 years or older, permanent residents; (2) Voluntarily participate in this study and sign the informed consent form; (3) Able to comply with the requirements of the clinical study protocol.

     Exclusion Criteria:Study participants with any of the following conditions shall not be enrolled in the study:

  1. Pre-vaccination laboratory test parameters with clinically meaningful abnormalities as specified in the protocol (Phase I only); (2) History of varicella vaccination or herpes zoster vaccination (including marketed vaccines and investigational vaccines); (3) Current herpes zoster infection or history of herpes zoster; (4) Close contact with varicella/herpes zoster patients within 30 days prior to the first dose; (5) Use of blood products or immunoglobulins within 3 months prior to the first dose, or planned use of blood products or immunoglobulins during the study period; (6) Use of other investigational or unregistered products (drugs or vaccines) within 1 month prior to the first dose, or planned participation in other clinical trials during this study; (7) Immunodeficiency or impairment, including but not limited to: primary immunodeficiency diseases, active autoimmune diseases (e.g., systemic lupus erythematosus, active rheumatoid arthritis, severe psoriasis, etc.), HIV infection, asplenia or functional asplenia, lymphoma, leukemia, etc.; (8) Receipt of immunosuppressive agents or other immunomodulators within 3 months prior to the first dose or planned use during the study period, such as long-term systemic corticosteroid therapy (oral/intravenous prednisone or equivalent for a total duration of more than 2 weeks), steroid pulse therapy (inhaled or topical use is not restricted), chemotherapy, radiotherapy, anti-rejection therapy after organ transplantation, etc.; (9) Allergy to any component of the investigational vaccine, or history of severe reactions to any vaccine or drug, e.g., urticaria, eczema, dyspnea, angioedema, etc.; (10) Presence of major diseases or major potential diseases that may interfere with or preclude completion of the study (e.g., severe cardiovascular and cerebrovascular diseases: cor pulmonale, pulmonary edema, uncontrolled hypertension [systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg], myocardial infarction/stroke within the past 12 months, NYHA Class III/IV; severe hepatic or renal diseases: e.g., decompensated cirrhosis, renal insufficiency on dialysis or imminently requiring dialysis, etc.; diabetes with severe complications; history of major organ transplantation; active malignancy, etc.); (11) Thrombocytopenia or other coagulation disorders (which may constitute contraindications to intramuscular injection); (12) Pregnant or lactating women; (13) Inability to ensure effective contraception from the time of signing informed consent to 3 months after completion of full vaccination series (effective contraceptive measures include: oral/injectable/implantable contraceptives, intrauterine devices, barrier methods (male/female condoms) with spermicides, partner surgical sterilization, or complete abstinence); (14) History of severe or active psychiatric and neurological diseases, including but not limited to: uncontrolled epilepsy, progressive neuropathy, history of Guillain-Barré syndrome, demyelinating diseases, post-encephalitis/myelitis with significant functional impairment, etc.; (15) Any other condition judged by the investigator as potentially affecting study evaluation, making the participant unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I clinical trial - low-dose adjuvanted vaccine group; Subjects will receive 2 doses of the recombinant herpes zoster adjuvanted vaccine at a 30-day interval. Main components: 50 μg of varicella-zoster virus glycoprotein E (gE) per 0.5 mL, and 375 μg of ZFA01 adjuvant per 0.5 mL.	Biological: Low-dose adjuvanted recombinant zoster vaccine; 0.5 mL per dose, containing 50 μg varicella-zoster virus glycoprotein E (gE) plus 375 μg adjuvant, intramuscular administration, 2 doses at Day 0 and Day 30.
Experimental: Phase I clinical trial - High-dose adjuvanted vaccine group; Subjects will receive 2 doses of the recombinant herpes zoster adjuvanted vaccine at a 30-day interval. Main components: 50 μg of varicella-zoster virus glycoprotein E (gE) per 0.5 mL, and 750 μg of ZFA01 adjuvant per 0.5 mL.	Biological: High-dose adjuvanted recombinant zoster vaccine (0 and 30 days schedule); 0.5 mL per dose, containing 50 μg varicella-zoster virus glycoprotein E (gE) plus 750 μg adjuvant, intramuscular administration, 2 doses at Day 0 and Day 30.
Placebo Comparator: Phase I clinical trial - Low-dose adjuvant placebo group; Subjects will receive 2 doses of the recombinant herpes zoster adjuvanted vaccine at a 30-day interval. Main component: 375 μg of ZFA01 adjuvant per 0.5 mL.	Biological: Low-dose adjuvant placebo; 0.5 mL per dose, containing 375 μg adjuvant only, no varicella-zoster virus glycoprotein E (gE), intramuscular administration, 2 doses at Day 0 and Day 30.
Placebo Comparator: Phase I clinical trial - High-dose adjuvant placebo group; Subjects will receive 2 doses of the recombinant herpes zoster adjuvanted vaccine at a 30-day interval. Main component: 750 μg of ZFA01 adjuvant per 0.5 mL.	Biological: High-dose adjuvant placebo; 0.5 mL per dose, containing 750 μg adjuvant only, no varicella-zoster virus glycoprotein E (gE), intramuscular administration, 2 doses at Day 0 and Day 30.
Experimental: Phase II clinical trial - adjuvanted vaccine group 1; Subjects will receive 2 doses of the recombinant herpes zoster adjuvanted vaccine at a 30-day interval. Main components: 50 μg of varicella-zoster virus glycoprotein E (gE) per 0.5 mL, and 750 μg of ZFA01 adjuvant per 0.5 mL.	Biological: Low-dose adjuvanted recombinant zoster vaccine; 0.5 mL per dose, containing 50 μg varicella-zoster virus glycoprotein E (gE) plus 375 μg adjuvant, intramuscular administration, 2 doses at Day 0 and Day 30.
Experimental: Phase II clinical trial - adjuvanted vaccine group 2; Subjects will receive 2 doses of the recombinant herpes zoster adjuvanted vaccine at a 60-day interval. Main components: 50 μg of varicella-zoster virus glycoprotein E (gE) per 0.5 mL, and 750 μg of ZFA01 adjuvant per 0.5 mL.	Biological: High-dose adjuvanted recombinant zoster vaccine (0 and 60 days schedule); 0.5 mL per dose, containing 50 μg varicella-zoster virus glycoprotein E (gE) plus 750 μg adjuvant, intramuscular administration, 2 doses at Day 0 and Day 60.
Placebo Comparator: Phase II clinical trial - positive control group (GlaxoSmithKline Biologicals SA); Subjects will receive 2 doses of the recombinant herpes zoster adjuvanted vaccine at a 60-day interval. Main component: 50 μg of varicella-zoster virus glycoprotein E (gE) per 0.5 mL. Main components: 50 μg of Quillaja saponaria saponin QS-21 per 0.5 mL, 50 μg of 3-O-desacyl-4'-monophosphoryl lipid A per 0.5 mL, 1 mg of dioleoylphosphatidylcholine per 0.5 mL, and 0.25 mg of cholesterol per 0.5 mL.	Biological: Zoster Vaccine Recombinant, Adjuvanted; 0.5 mL per dose, containing 50 μg varicella-zoster virus glycoprotein E (gE), adjuvanted with AS01B, intramuscular administration, 2 doses at Day 0 and Day 60.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Endpoints(1):Occurrence of all AEs	Occurrence of all adverse events (AEs) within 30 days after each dose of vaccination (number of episodes, number of cases, incidence rate, severity, and relationship to the investigational vaccine): Occurrence of AEs within 30 minutes after each dose of vaccination;; Occurrence of solicited AEs within 0-14 days after each dose of vaccination;; Occurrence of unsolicited AEs within 30 days after each dose of vaccination.	within 30 days after each dose of vaccination
Safety Endpoints(2):Occurrence of all SAEs	Occurrence of all SAEs from the first dose up to 12 months after completion of the full vaccination series (number of cases, number of episodes, incidence rate, and relationship to the investigational vaccine).	from the first dose up to 12 months after completion of the full vaccination series
Safety Endpoints(3):Occurrence of all pIMDs	Occurrence of all potential immune-mediated disorders (pIMDs) from the first dose up to 12 months after completion of the full vaccination series (number of episodes, number of cases, incidence rate, severity, and relationship to the investigational vaccine).	from the first dose up to 12 months after completion of the full vaccination series
Immunogenicity Endpoints (1): GMTs of VZV gE antibody and VZV antibody	Humoral Immunity: (1) GMTs of VZV gE antibody and VZV antibody at pre-first dose, 30 days after completion of full vaccination series, and 6 and 12 months after completion of full vaccination series	at pre-first dose, 30 days after completion of full vaccination series, and 6 and 12 months after completion of full vaccination series
Immunogenicity Endpoints (2): GMIs of VZV gE antibody and VZV antibody	Humoral Immunity: (2) GMIs of VZV gE antibody and VZV antibody at 30 days, 6 months, and 12 months after completion of full vaccination series	at 30 days, 6 months, and 12 months after completion of full vaccination series
Immunogenicity Endpoints (3): Seropositivity rates of VZV gE antibody and VZV antibody	Humoral Immunity: (3) Seropositivity rates of VZV gE antibody and VZV antibody at pre-first dose, 30 days after completion of full vaccination series, and 6 and 12 months after completion of full vaccination series	at pre-first dose, 30 days after completion of full vaccination series, and 6 and 12 months after completion of full vaccination series
Immunogenicity Endpoints (4): Seroconversion rates of VZV gE antibody and VZV antibody.	Humoral Immunity: (4) Seroconversion rates of VZV gE antibody and VZV antibody at 30 days after completion of full vaccination series	at 30 days after completion of full vaccination series
Immunogenicity Endpoints (5): Detection frequency of CD4²⁺ T cells secreting at least two gE-specific cytokines (IFN-γ, IL-2, TNF-α, CD40L, IL-17A)	Cellular immunity: Detection frequency of CD4²⁺ T cells secreting at least two gE-specific cytokines (IFN-γ, IL-2, TNF-α, CD40L, IL-17A) at pre-first dose, 30 days after completion of full vaccination series, and 6 and 12 months after completion of full vaccination series.	at pre-first dose, 30 days after completion of full vaccination series, and 6 and 12 months after completion of full vaccination series
Percentage of Participants With Clinically Significant Serum Chemistry Laboratory Abnormalities	Proportion of participants with clinically meaningful abnormalities in serum chemistry parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), fasting glucose (GLU), creatinine (CRE), assessed according to CTCAE v5.0 criteria, compared with pre-vaccination baseline.	Pre-vaccination (Baseline), Day 4 after the first dose
Percentage of Participants With Clinically Significant Hematology Laboratory Abnormalities	Proportion of participants with clinically meaningful abnormalities in hematology parameters, including hemoglobin (HGB), red blood cell count (RBC), white blood cell count (WBC), platelet count (PLT), assessed according to CTCAE v5.0 criteria, compared with pre-vaccination baseline.	Pre-vaccination (Baseline), Day 4 after the first dose
Percentage of Participants With Clinically Significant Urinalysis Laboratory Abnormalities	Proportion of participants with clinically meaningful abnormalities in urinalysis parameters, including urine protein (PRO), urine red blood cell (RBC), assessed according to CTCAE v5.0 criteria, compared with pre-vaccination baseline.	Pre-vaccination (Baseline), Day 4 after the first dose
Percentage of Participants With Clinically Significant Coagulation Laboratory Abnormalities	Proportion of participants with clinically meaningful abnormalities in coagulation parameters, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), international normalized ratio (INR), assessed according to CTCAE v5.0 criteria, compared with pre-vaccination baseline.	Pre-vaccination (Baseline), Day 4 after the first dose

Collaborators and Investigators

• Sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): November 10, 2026
• Primary Completion (Estimated): May 23, 2029
• Study Completion (Estimated): May 23, 2029

Study Registration Dates

• First Submitted: October 21, 2026
• First Submitted That Met QC Criteria: November 3, 2026
• First Posted (Actual): November 5, 2026

Study Record Updates

• Last Update Posted (Actual): November 5, 2026
• Last Update Submitted That Met QC Criteria: November 3, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: prevention
• Additional Relevant MeSH Terms: Varicella Zoster Virus Infection; Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Herpes Zoster; Organization and Administration; Health Services Administration; Appointments and Schedules
• Other Study ID Numbers: LKM-2025-HZV02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No